Lymphoma treatment at cross-roads; era of immunotherapy and new paradigms for more cancer cures

Predicting response to CAR-T cell therapy in lymphoma patients

Lymphoma is a the most common type of blood cancer, and unlike many other cancer types, its incidence is currently increasing in Canada. Non-Hodgkin lymphoma (NHL) patients typically receive chemotherapy and sometimes radiation or a targeted treatment using a monoclonal antibody medication.  

In recent years, a new kind of treatment called CAR-T therapy has started being used to treat some lymphoma patients for whom these treatments are not successful. CAR-T therapy makes use of an innovative technology called chimeric antigen receptor T (CAR-T) cells, in which the patient's own T cells are engineered to attack tumour cells. T cells are a type of immune cell; CAR-T therapy therefore falls under the umbrella of immunotherapy. 

While CAR-T therapy works very well for some patients, others show little or no response. However, it is currently not possible to predict which lymphoma patients may benefit from this expensive treatment. 

To try to identify patients most likely to benefit from CAR-T therapy, the Marathon of Hope Cancer Centres Network (MOHCCN) is funding a team of pan-Canadian researchers in Montréal, Winnipeg, Hamilton, Ottawa, Toronto, and Québec to collect clinical data and sequence the whole genome and transcriptome of tumour cells from NHL patients. The team is led by Dr. Lambert Busque, a hematologist and the director of the Clinical Laboratory for Molecular Diagnosis and the Hematopoiesis and Aging Research Unit at hôpital Maisonneuve-Rosemont and professor at Université de Montréal. 

This pan-Canadian project has two major aims: (1) to identify NHL patients who are likely to fail traditional therapies and who would benefit from receiving CAR-T therapy earlier on; and (2) to identify features that predict whether an NHL patient is likely to respond to CAR-T therapy. 

“A national approach is required to study CAR-T outcomes in the Canadian context", says Dr. Busque. “At this time, we do not know who will benefit from this expensive treatment. We need the tools to personalize CAR-T cell therapy". 

As part of the study, funds from other sources will also be used to gather additional information about the characteristics of participating patients’ tumour cells and T cells. By using artificial intelligence (AI) approaches to analyze this large dataset, the team seeks to uncover new ways of identifying which kind of therapy is most likely to be effective against individual NHL patients’ specific cancer. 

Dr. Busque emphasizes that this work “has the potential to change the paradigm of lymphoma management in Canada” by enabling personalized treatments for NHL patients, minimizing unnecessary treatments and optimizing outcomes. 

Broadening impact 

MOHCCN funding for this project comes from the Network's Pan-Canadian Projects program, which aims to unite researchers and clinicals from multiple provinces to accelerate precision oncology research in Canada. 

As part of this initiative, Dr Busque and the research team have committed to contributing all the clinical and genomic data collected through the study to the MOHCCN Gold Cohort, which is on track to become the largest and most complete cancer case resource in Canada. This dataset will enable further research projects that seek to advance precision oncology care across cancer types, both within Canada and globally.